A PTEN inhibitor displays preclinical activity against hepatocarcinoma cells

Cell Cycle
Giuseppa AugelloMelchiorre Cervello

Abstract

Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32-44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability when combined with PI3K/mTOR and RAF/MEK/ERK pathway inhibitors, but only in Hep3B cells, and significantly inhibited tumor growth in nude mice bearing xenografts of Hep3B cells. Therefore, we demonstrated for the first time that VO-OHpic inhibited cell growth and induced senescence in HCC cells with low PTEN expression, and that the combination of VO-OHpic with PI3K/mTOR and RAF/MEK/ERK inhibitors resulted in a more effective tumor cell kill. Our findings, hence, provide proof-of-principle evidence that pharmacological inhibition of PTEN ma...Continue Reading

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Citations

Oct 26, 2016·Advances in Biological Regulation·James A McCubreyLinda S Steelman
Feb 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rafael Pulido
Jul 12, 2016·Biomarkers in Cancer·Ranjit Chauhan, Nivedita Lahiri
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Mar 28, 2021·Translational Psychiatry·Xiao-Qing WangYu-Qiang Ding
Aug 3, 2021·Cell Regeneration·Tian LiangJinghai Chen

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flow cytometry
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Software Mentioned

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